Posted on 06/19/2017 10:34:26 AM PDT by Red Badger
BALTIMORE (TNS) Hasini Jayatilaka was a sophomore at the Johns Hopkins University working in a lab studying cancer cells when she noticed that when the cells become too densely packed, some would break off and start spreading.
She wasnt sure what to make of it, until she attended an academic conference and heard a speaker talking about bacterial cells behaving the same way. Yet when she went through the academic literature to see if anyone had written about similar behavior in cancer cells, she found nothing.
Seven years later, the theory Jayatilaka developed early in college is now a bona fide discovery that offers significant promise for cancer treatment.
Jayatilaka and a team at Johns Hopkins discovered the biochemical mechanism that tells cancer cells to break off from the primary tumor and spread throughout the body, a process called metastasis. Some 90 percent of cancer deaths are caused when cancer metastasizes. The team also found that two existing, FDA-approved drugs can slow metastasis significantly.
A female patient with breast cancer doesnt succumb to the disease just because she has a mass on her breast; she succumbs to the disease because (when) it spreads either to the lungs, the liver, the brain, it becomes untreatable, said Jayatilaka, who earned her doctorate in chemical and biomolecular engineering this spring in addition to her earlier undergraduate degree at Hopkins.
There are really no therapeutics out there right now that directly target the spread of cancer. So what we came up with through our studies was this drug cocktail that could potentially inhibit the spread of cancer.
The study was published online May 26 in the journal Nature Communications. The next step for the team is to test the effectiveness of the drugs in human subjects.
Typically, cancer research and treatment has focused on shrinking the primary tumor through chemotherapy or other methods. But, the team said, by attacking the deadly process of metastasis, more patients could survive.
Its not this primary tumor thats going to kill you typically, said Denis Wirtz, Johns Hopkins vice provost for research and director of its Physical Sciences-Oncology Center, who was a senior author on the paper.
Jayatilaka began by studying how cancer cells behave and communicate with each other, using a three-dimensional model that mimics human tissue rather than looking at them in a petri dish. Many researchers believe metastasis happens after the primary tumor reaches a certain size, but Jayatilaka found it was the tumors density that determined when it would metastasize.
If you look at the human population, once we become too dense in an area, we move out to the suburbs or wherever, and we decide to set up shop there, Jayatilaka said. I think the cancer cells are doing the same thing.
When the tumor reaches a certain density, the study found, it releases two proteins called Interleukin 6 and Interleukin 8, signaling to cancer cells that things had grown too crowded and it was time to break off and head into other parts of the body.
Previously, Wirtz said, the act of a tumor growing and the act of cancer cells spreading were thought to be very separate activities, because thats how it appeared by studying cancer cells in a petri dish, rather than the 3-D model the Hopkins team used. Many researchers study only cancer cell growth or its spread, and dont communicate with each other often, he said.
Once the cancer cells start to sense the presence of too many other cancer cells around them, they start secreting the Interleukin proteins, Wirtz said. If those proteins are added to a tumor that hasnt yet metastasized, that process would begin, he said.
The team then tested two drugs known to work on the Interleukin receptors to see if they would block or slow metastasis in mice. They found that using the two drugs together would block the signals from the Interleukin proteins that told the cancer cells to break off and spread, slowing though not completely stopping metastasis.
The drugs the team used were Tocilizumab, a rheumatoid arthritis treatment, and Reparixin, which is being evaluated for cancer treatment.
The drugs bind to the Interleukin receptors and block their signals, slowing metastasis.
Though metastasis was not completely stopped, Jayatilaka said, the mice given the drug cocktail fared well and survived through the experiment. She said adding another, yet-to-be-determined drug or tweaking the dose might stop metastasis entirely.
Contrary to the hair loss, nausea and other negative side effects patients undergoing chemotherapy suffer, Wirtz said the side effects from the drugs used in the study would be minimal.
Anirban Maitra, co-director of a pancreatic cancer research center at the MD Anderson Cancer Center at the University of Texas, cautioned that clinical trials in humans are needed to prove the theory.
Theres a risk that something that looks so great in an animal model wont pan out in a human, he said.
But Maitra said the study looked promising, in particular because the researchers had used drugs already on the market. It can take a decade to identify a drug that would perform similarly and get it approved, and many similar observations dont advance because of the time and expense it can take to get drug approval, he said.
Muhammad Zaman, a professor and cancer expert at Boston University, called the Hopkins discovery exciting.
This paper gives you a very specific target to design drugs against, he said. Thats really quite spectacular from the point of view of drug design and creating therapies.
Zaman said it was important for cancer researchers to use engineering to better understand cancer, as the Hopkins team did.
This really brings cancer and engineering together in a very unique way, and it really takes an approach that is quantitative and rigorous, he said. We have to think of cancer as a complex system, not just a disease.
Wirtz predicted a future where cancer would be fought with a mix of chemotherapy to shrink the primary tumor and drug cocktails like the one the Hopkins team developed to ensure it would not metastasize. He compared such a treatment to how HIV/AIDS is treated today.
Were not going to cure cancer with one therapy or even two therapies; its going to be drug cocktails, Wirtz said. Thats what saved the day with HIV/AIDS.
Immunotherapy, which uses the bodys immune system to fight cancer, also could play a role in a combined method, Wirtz added.
Were, in research, sometimes incentivized to look at one pathway at a time, one type of cancer at a time, Wirtz said. I think oncology has started realizing were going to need more than one approach.
In my case they cut very deep and about three hours before the surgery they pumped in some radioactive material and then tested my whole arm but especially my lymph glands with a geiger counter. They removed a couple of the glands and sent the whole mess to the lab. They then did a pet scan a few weeks later to see whether anything lit up. At the time (11 years ago) there was no cure for melanoma except cutting the tumor out. It all worked for me but I have a pretty high chance of it showing up again.
I’ve dealt with metastatic cancer twice in my life, never in my person. Once with a family member and once with a beloved dog. I can say that certain antibiotics are regarded as potentially effective therapy in preventing or slowing metastasis in certain cancers, so there is precedent for this sort of thinking that goes back at least a decade. I think many cancers are ultimately viral in origin myself, though.
Sounds like you had excellent doctors... and eleven years? That's wonderful. 'Five years' is considered a cure, right? God Bless you Mercat.
>> Who suggested you use Avastin for your macular degeneration? <<
I’ve had a couple of eye injections with Avastin, both performed by a retina specialist ophthalmologist. He’s a recognized expert on the matter, and I was referred to him by my “regular” ophthalmologist.
Moreover, Avastin is now used very commonly in this application — in spite of the fact that the FDA has never formally approved it for macular degeneration.
In other words, hooray for off-label uses!
Thanks for the info. MD runs in my family so I’ll make note of this.
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